The neuropathology Core will provide, to the researchers of the Program Project, brain tissue and diagnostic neuropathology evaluations on Alzheimer's disease (AD) patients and controls, from subjects who have been closely followed in the Clinical Core with neurological and neuropsychological examinations. Brain tissue with minimal post-mortem intervals will be obtained and preserved so as to fill the needs of the three Program Project investigators. The abundant brain tissue received by the Rush Brain Bank from the Rush Alzheimer's Disease Center (RADC) and the establishment of new sources of control tissue, the Religious Order Study (ROS) and the RADC control program will allow the Neuropathology Core to fulfill the needs of the investigators. Each project will study a series of clinically defined brains': 8 controls without dementia and 24 AD patients divided equally between three groups; mild, moderate and severe cognitive impairment. One project will use fixed basal forebrain tissue and snap frozen cortical tissue, for immunohistochemical and in situ hybridization studies. Other projects will use fixed and snap frozen basal forebrain and temporal lobe tissue for immunohistochemistry, in situ hybridization, receptor binding and radioimmunoassay studies. The RADC will be the primary source of the moderately and severely impaired AD patients, and the RADC control study ad the Religious Order Study will be the source of the mildly impaired AD patients and control subjects. A thorough neuropathological evaluation will be performed on each case using standard diagnostic criteria for Alzheimer's disease (NIH consensus criteria), Parkinson's disease (CERAD), and related disorders. A direct entry data program will be used for all gross and microscopic neuropathological information. With the use of a specimen tracking software program (FreezerWorks), all tissue will be accurately indexed allowing rapid and reliable distribution of tissue to investigators. Close linkage will be maintained with the clinical core through monthly meetings to facilitate tissue distribution. The brain tissue and neuropathological data provided to investigators by the Neuropathology Core is critical for the success of the projects and for the provision of seminal information about nerve growth factor trophism, galanin remodeling, and altered tau conformation and the progression of Alzheimer's disease.